Mycotic infections are ubiquitously distributed geographically and amongst individuals of all age groups. Recent reports indicate that systemic mycoses will continue to be a major health problem and actually increase as immunosuppressive therapies proliferate attendant to treatment of patients with malignant and immunologically related diseases or with organ transplants. The major chemotherapeutic drugs currently employed, and those in experimental and developmental programs, have as their principal target some aspect of the sterol physiology of the fungi. It is clear that the distinctive sterol structures and functions in the fungi represent particularly vulnerable targets for controlling fungal growth. The proposed research is a basic program of study of the sterols in fungi. Yeast have been shown to be a nearly ideal system for this work. The long term goal is to identify cellular reactions that are unique to the fungi or are especially amenable to therapeutic control. The objective of the requested grant is to develop an understanding of sterol biosynthesis and metabolism and to study their physiological function and control. It is anticipated that this information will be of use in the development of specific controlling agents for various pathogenic fungi.